Nonparametric location-scale models for censored successive survival times

Let (T₁,T₂) be gap times corresponding to two consecutive events, which are observed subject to (univariate) random right-censoring. The censoring variable corresponding to the second gap time T₂ will in general depend on this gap time. Suppose the vector (T₁,T₂) satisfies the nonparametric location-scale regression model T₂=m(T₁)+σ(T₁)?, where the functions m and σ are ‘smooth’, and ? is independent of T₁. The aim of this paper is twofold. First, we propose a nonparametric estimator of the distribution of the error variable under this model. This problem differs from others considered in the recent related literature in that the censoring acts not only on the response but also on the covariate, having no obvious solution. On the basis of the idea of transfer of tail information (Van Keilegom and Akritas, 1999), we then use the proposed estimator of the error distribution to introduce nonparametric estimators for important targets such as: (a) the conditional distribution of T₂ given T₁; (b) the bivariate distribution of the gap times; and (c) the so-called transition probabilities. The asymptotic properties of these estimators are obtained. We also illustrate through simulations, that the new estimators based on the location-scale model may behave much better than existing ones.     

Robust estimation in accelerated failure time models

Lifetime Data Analysis - The accelerated failure time model is widely used for analyzing censored survival times often observed in clinical studies. It is well-known that the ordinary maximum...     

Asymptotic expansions and the reliability of tests in accelerated failure time models

This paper gives matrix formilae for the O(n^-1 ) cerrecti0n applicable to asymptotically efficient conditional moment tests. These formulae only require expectations of functions involving, at most, second order derivatives of the log-likelihood; unlike those previously providcd by Ferrari and Corddro(1994). The correction is used to assess the reliability of first order asymptotic theory for arbitrary residual-based diagnostics in a class of accelerated failure time models: this correction is always parameter free, depending only on the number of included covariates in the regression design. For all but one of the tests considered, first order theory is found to be extremely unreliable, even in quite large samples, although this may not be widely appreciated by applied workers.     

Accelerated failure time models for the analysis of competing risks

Competing risks are common in clinical cancer research, as patients are subject to multiple potential failure outcomes, such as death from the cancer itself or from complications arising from the disease. In the analysis of competing risks, several regression methods are available for the evaluation of the relationship between covariates and cause-specific failures, many of which are based on Cox’s proportional hazards model. Although a great deal of research has been conducted on estimating competing risks, less attention has been devoted to linear regression modeling, which is often referred to as the accelerated failure time (AFT) model in survival literature. In this article, we address the use and interpretation of linear regression analysis with regard to the competing risks problem. We introduce two types of AFT modeling framework, where the influence of a covariate can be evaluated in relation to either a cause-specific hazard function, referred to as cause-specific AFT (CS-AFT) modeling in this study, or the cumulative incidence function of a particular failure type, referred to as crude-risk AFT (CR-AFT) modeling. Simulation studies illustrate that, as in hazard-based competing risks analysis, these two models can produce substantially different effects, depending on the relationship between the covariates and both the failure type of principal interest and competing failure types. We apply the AFT methods to data from non-Hodgkin lymphoma patients, where the dataset is characterized by two competing events, disease relapse and death without relapse, and non-proportionality. We demonstrate how the data can be analyzed and interpreted, using linear competing risks regression models.     

Additive transformation models for clustered failure time data

We propose a class of additive transformation risk models for clustered failure time data. Our models are motivated by the usual additive risk model for independent failure times incorporating a frailty with mean one and constant variability which is a natural generalization of the additive risk model from univariate failure time to multivariate failure time. An estimating equation approach based on the marginal hazards function is proposed. Under the assumption that cluster sizes are completely random, we show the resulting estimators of the regression coefficients are consistent and asymptotically normal. We also provide goodness-of-fit test statistics for choosing the transformation. Simulation studies and real data analysis are conducted to examine the finite-sample performance of our estimators.     

Empirical likelihood method for the multivariate accelerated failure time models

In applications, multivariate failure time data appears when each study subject may potentially experience several types of failures or recurrences of a certain phenomenon, or failure times may be clustered. Three types of marginal accelerated failure time models dealing with multiple events data, recurrent events data and clustered events data are considered. We propose a unified empirical likelihood inferential procedure for the three types of models based on rank estimation method. The resulting log-empirical likelihood ratios are shown to possess chi-squared limiting distributions. The properties can be applied to do tests and construct confidence regions without the need to solve the rank estimating equations nor to estimate the limiting variance-covariance matrices. The related computation is easy to implement. The proposed method is illustrated by extensive simulation studies and a real example.     

Ancillarity properties of generalized residuals with applications in failure time models

This paper addresses the issue of when residuals from failure time models, which are useful in model validation and diagnostics, possess a conditional ancillarity property. This property states that the distribution of the residuals depends on the model parameters only through a many-to-one function of these parameters, which in certain models turn out to be the censoring proportion. Concrete results are obtained for models which possess an invariance structure, and these results are applied to commonly used failure time models. Aside from furthering our understanding of the distributional structure of residuals, this conditional ancillarity property can be exploited to study in a more efficient manner the distributional properties of residuals either analytically and/or through numerical methods.     

Properties of test statistics applied to residuals in failure time models

Asymptotic properties of a class of test statistics when applied to hazard-based residuals arising in survival and reliability models are presented. These test statistics are useful in goodness-of-fit tests and model validation. The properties are obtained by examining the asymptotic properties of generalized residual processes, which are (possibly random) time transformations of the processes associated with the incomplete failure times. Since the time transformations depend on unknown model parameters, the residual processes are obtained by replacing the unknown parameters by their estimators. The results shed light on the effects of estimating parameters to obtain the residual processes. Implications concerning possible pitfalls of some existing model validation procedures utilizing hazard-based residuals and ways to correct these problems are discussed.     

A study of R2 measure under the accelerated failure time models

For right-censored data, the accelerated failure time (AFT) model is an alternative to the commonly used proportional hazards regression model. It is a linear model for the (log-transformed) outcome of interest, and is particularly useful for censored outcomes that are not time-to-event, such as laboratory measurements. We provide a general and easily computable definition of the R² measure of explained variation under the AFT model for right-censored data. We study its behavior under different censoring scenarios and under different error distributions; in particular, we also study its robustness when the parametric error distribution is misspecified. Based on Monte Carlo investigation results, we recommend the log-normal distribution as a robust error distribution to be used in practice for the parametric AFT model, when the R² measure is of interest. We apply our methodology to an alcohol consumption during pregnancy data set from Ukraine.     

Estimation,prediction and interpretation of NGG random effects models: an application to Kevlar fibre failure times

We propose a class of Bayesian semiparametric mixed-effects models; its distinctive feature is the randomness of the grouping of observations, which can be inferred from the data. The model can be viewed under a more natural perspective, as a Bayesian semiparametric regression model on the log-scale; hence, in the original scale, the error is a mixture of Weibull densities mixed on both parameters by a normalized generalized gamma random measure, encompassing the Dirichlet process. As an estimate of the posterior distribution of the clustering of the random-effects parameters, we consider the partition minimizing the posterior expectation of a suitable class of loss functions. As a merely illustrative application of our model we consider a Kevlar fibre lifetime dataset (with censoring). We implement an MCMC scheme, obtaining posterior credibility intervals for the predictive distributions and for the quantiles of the failure times under different stress levels. Compared to a previous parametric Bayesian analysis, we obtain narrower credibility intervals and a better fit to the data. We found that there are three main clusters among the random-effects parameters, in accordance with previous frequentist analysis.     

A martingale-based test for independence of time to failure and cause of failure for competing risks models

In this article, we introduce a class of tests, using a martingale approach, for testing independence of failure time and cause of failure for competing risks data. Asymptotic distribution of the proposed test statistic is derived. The procedure is illustrated with a real-life data. A simulation study is carried out to assess the level and power of the test.     

Bayesian analysis under accelerated failure time models with error-prone time-to-event outcomes

Lifetime Data Analysis - We consider accelerated failure time models with error-prone time-to-event outcomes. The proposed models extend the conventional accelerated failure time model by allowing...     

Correcting for non-compliance in randomized trials using rank preserving structural failure time models

We propose correcting for non-compliance in randomized trials by estimating the parameters of a class of semi-parametric failure time models, the rank preserving structural failure time models, using a class of rank estimators. These models are the structural or strong version of the “accelerated failure time model with time-dependent covariates” of Cox and Oakes (1984). In this paper we develop a large sample theory for these estimators, derive the optimal estimator within this class, and briefly consider the construction of “partially adaptive” estimators whose efficiency may approach that of the optimal estimator. We show that in the absence of censoring the optimal estimator attains the semiparametric efficiency bound for the model.     

Joint modelling of event counts and survival times

Summary.  In studies of recurrent events, such as epileptic seizures, there can be a large amount of information about a cohort over a period of time, but current methods for these data are often unable to utilize all of the available information. The paper considers data which include post-treatment survival times for individuals experiencing recurring events, as well as a measure of the base-line event rate, in the form of a pre-randomization event count. Standard survival analysis may treat this pre-randomization count as a covariate, but the paper proposes a parametric joint model based on an underlying Poisson process, which will give a more precise estimate of the treatment effect.